A heterozygote advantage (heterozygous advantage) describes the case in which the heterozygote genotype has a higher relative fitness than either the homozygote dominant or homozygote recessive genotype. The specific case of heterozygote advantage due to a single locus is known as overdominance. In more general terms, overdominance is a condition in genetics where the phenotype of the heterozygote lies outside of the phenotypical range of both homozygote parents, and heterozygous individuals have a higher fitness than homozygous individuals.
Polymorphism can be maintained by selection favoring the heterozygote, and this mechanism is used to explain the occurrence of some kinds of genetic variability. A common example is the case where the heterozygote conveys both advantages and disadvantages, while both homozygotes convey a disadvantage. A well-established case of heterozygote advantage is that of the gene involved in sickle cell anaemia.
Often, the advantages and disadvantages conveyed are rather complicated, because more than one gene may influence a given trait or morph. Major genes almost always have multiple effects (pleiotropism), which can simultaneously convey separate advantageous traits and disadvantageous traits upon the same organism.
In this instance, the state of the organism's environment will provide selection, with a net effect either favoring or working in opposition to the gene, until an environmentally determined equilibrium is reached.
Heterozygote advantage is a major underlying mechanism for heterosis, or "hybrid vigor", which is the improved or increased function of any biological quality in a hybrid offspring. Previous research, comparing measures of dominance, overdominance and epistasis (mostly in plants), found that the majority of cases of heterozygote advantage were due to complementation (or dominance), the masking of deleterious recessive alleles by wild-type alleles, as discussed in the articles Heterosis and Complementation (genetics), but there were also findings of overdominance, especially in rice. More recent research, however, has established that there is also an epigenetic contribution to heterozygote advantage, primarily as determined in plants, though also reported in mice.